title: A repeat-dose thorough QT study of inhaled fluticasone furoate/vilanterol combination in healthy subjects.
abstract: OBJECTIVE
  This study was designed as a thorough QT (TQT) study to evaluate the effects of fluticasone furoate (FF)/vilanterol (VI) in healthy subjects. Supportive data from a TQT study conducted with FF are also presented.
  
  
  METHODS
  This was a randomized, placebo- and positive-controlled, double-dummy, double-blind, four-way crossover study, in which healthy subjects (n = 85) were randomized to 7 days of once-daily treatment of FF/VI (200/25 or 800/100 μg) or placebo or single-dose oral moxifloxacin (single-blind, 400 mg). In the supportive TQT study, subjects (n = 40) were randomized to single-dose inhaled FF (4000 μg), oral moxifloxacin (400 mg) or placebo.
  
  
  RESULTS
  There was a lack of effect of FF/VI (200/25 μg) on QTcF (Fridericia's correction); all time-matched mean differences from baseline relative to placebo (0-24 h) were <5 ms, with upper 90% confidence intervals (CI) of <10 ms. At 800/100 μg, FF/VI had no significant clinical effect on QTcF except at 30 min postdose when the 90% CI was >10 ms [mean (90% CI), 9.6 ms (7.2, 12.0)]. No effect on QTci (individually corrected) was observed at either strength of FF/VI, with mean time-matched treatment differences <5 ms at all time points [upper 90% CIs <10 ms (0-24 h)]. Assay sensitivity was confirmed; moxifloxacin prolonged QTcF and QTci, with time-matched mean differences from baseline relative to placebo of >10 ms (1-8 h postdose).
  
  
  CONCLUSIONS
  Repeat once-daily dosing of FF/VI (200/25 μg), which is the highest therapeutic strength used in phase III studies, is not associated with QTc prolongation in healthy subjects. Supratherapeutic strength FF/VI (800/100 μg) demonstrated a small transient effect on QTcF but not on QTci.
authors.affiliation: Clinical Pharmacology, Global Clinical Respiratory Medicines Development Centre, GlaxoSmithKline, Stevenage, UK.
authors.forename: Rodger
authors.initials: R
authors.lastname: Kempsford
authors.forename: Ann
authors.initials: A
authors.lastname: Allen
authors.forename: Kathryn
authors.initials: K
authors.lastname: Kelly
authors.forename: Parminder
authors.initials: P
authors.lastname: Saggu
authors.forename: Courtney
authors.initials: C
authors.lastname: Crim
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000368:Aged; D000730:Androstadienes / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001592:Benzyl Alcohols / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D002722:Chlorobenzenes / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D064368:Healthy Volunteers; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008131:London; D008133:Long QT Syndrome / Q000139:chemically induced / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D018570:Risk Assessment; D055815:Young Adult
chemical_list: D000730:Androstadienes; D001592:Benzyl Alcohols; D001993:Bronchodilator Agents; D002722:Chlorobenzenes; D004338:Drug Combinations; D005938:Glucocorticoids; C550468:vilanterol; C523187:fluticasone furoate
keywords: fluticasone furoate; healthy subjects; moxifloxacin; thorough QT; vilanterol